title: Staphylokinase promotes the establishment of Staphylococcus aureus skin infections while decreasing disease severity.
abstract: Skin infections are frequently caused by Staphylococcus aureus and can lead to a fatal sepsis. The microbial mechanisms controlling the initiation and progression from mild skin infection to a severe disseminated infection remain poorly understood. Using a combination of clinical data and in vitro and ex vivo assays, we show that staphylokinase, secreted by S. aureus, promoted the establishment of skin infections in humans and increased bacterial penetration through skin barriers by activating plasminogen. However, when infection was established, the interaction between staphylokinase and plasminogen did not promote systemic dissemination but induced the opening and draining of abscesses and decreased disease severity in neutropenic mice. Also, increased staphylokinase production was associated with noninvasive S. aureus infections in patients. Our results point out the dual roles of staphylokinase in S. aureus skin infections as promoting the establishment of infections while decreasing disease severity.
authors.affiliation: Department of Rheumatology and Inflammation Research, Institute of Medicine, University of Gothenburg. Sweden. jakub.kwiecinski@rheuma.gu.se
authors.forename: Jakub
authors.initials: J
authors.lastname: Kwiecinski
authors.forename: Gunnar
authors.initials: G
authors.lastname: Jacobsson
authors.forename: Maria
authors.initials: M
authors.lastname: Karlsson
authors.forename: Xuefeng
authors.initials: X
authors.lastname: Zhu
authors.forename: Wanzhong
authors.initials: W
authors.lastname: Wang
authors.forename: Tomas
authors.initials: T
authors.lastname: Bremell
authors.forename: Elisabet
authors.initials: E
authors.lastname: Josefsson
authors.forename: Tao
authors.initials: T
authors.lastname: Jin
mesh_terms: D000038:Abscess / Q000382:microbiology; D000818:Animals; D015415:Biomarkers / Q000097:blood; D005260:Female; D015964:Gene Expression Regulation, Bacterial; D006801:Humans; D008297:Male; D008666:Metalloendopeptidases / Q000378:metabolism*; D051379:Mice; D010958:Plasminogen / Q000378:metabolism; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood; D010960:Plasminogen Activators / Q000494:pharmacology; D012867:Skin / Q000382:microbiology / Q000473:pathology; D012871:Skin Diseases / Q000382:microbiology* / Q000473:pathology; D013203:Staphylococcal Infections / Q000473:pathology*; D013211:Staphylococcus aureus / Q000201:enzymology
chemical_list: D015415:Biomarkers; D017395:Plasminogen Activator Inhibitor 1; D010958:Plasminogen; D010960:Plasminogen Activators; D008666:Metalloendopeptidases; C022653:auR protein, Staphylococcus aureus
keywords: mouse model; pathogen–host relation; plasminogen; skin infection; staphylococcus; staphylokinase